Calcium Pantothenate

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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C₁₈H₃₂CaN₂O₁₀ 476.53

β-Alanine, N-(2,4-dihydroxy-3,3-dimethyl-1-oxobutyl)-, calcium salt (2:1), (R)-;

Calcium d-pantothenate (1:2) CAS RN®: 137-08-6; UNII: 568ET80C3D.

1 DEFINITION

Calcium Pantothenate is the calcium salt of the dextrorotatory isomer of pantothenic acid. It contains NLT 98.0% and NMT 102.0% of calcium

pantothenate (C₁₈H₃₂CaN₂O₁₀), calculated on the dried basis.

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

B. Identification Tests—General 〈191〉, Chemical Identification Tests, Calcium

Sample solution: 50 mg/mL

Acceptance criteria: Meets the requirements

C. Optical Rotation 〈781S〉, Procedures, Specific Rotation

Sample solution: 50 mg/mL in water

Acceptance criteria: +25.0° to +27.5°

3 ASSAY

Change to read:

Procedure

Mobile phase: Dissolve 1.56 g of monobasic sodium phosphate in 900 mL of water, and adjust the pH to 2.5 with concentrated ortho-phosphoric acid. Add 10 mL of acetonitrile and dilute with water to 1000 mL.

System suitability solution: 0.04 mg/mL of USP Calcium Pantothenate RS and 0.1 mg/mL of USP Pantolactone RS in water

Standard solution: 0.5 mg/mL of USP Calcium Pantothenate RS in water

Sample solution: 0.5 mg/mL of Calcium Pantothenate in water

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 200 nm

Column: 3.0-mm × 15-cm; 3.5-μm packing L1

Column temperature: 35°

Flow rate: 1.2 mL/min

Injection volume: 5 μL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for pantolactone and pantothenic acid are 0.8 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 3.0 between pantolactone and pantothenic acid peaks, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of calcium pantothenate (C₁₈H₃₂CaN₂O₁₀) in the portion of Calcium Pantothenate taken:

Result = (r_U /r_S) × (C_S /C_U ) x 100

r_U = peak area of pantothenic acid from the Sample solution

r_S = peak area of pantothenic acid from the Standard solution

C_S = concentration of USP Calcium Pantothenate RS in the Standard solution (mg/mL)

C_U = concentration of Calcium Pantothenate in the Sample solution (mg/mL)

(USP 1-Dec-2023)

Acceptance criteria: 98.0%–102.0% on the dried basis

4 OTHER COMPONENTS

Content of Calcium

Sample: 800 mg of Calcium Pantothenate

Blank: 150 mL of water containing 2 mL of 3 N hydrochloric acid

Titrimetric system

(See Titrimetry 〈541〉.)

Mode: Direct titration

Titrant: 0.05 M edetate disodium VS

Endpoint detection: Visual

Analysis: Dissolve the Sample in 150 mL of water containing 2 mL of 3 N hydrochloric acid. Add 15 mL of 1 N sodium hydroxide and 300 mg of hydroxy naphthol blue, and titrate with Titrant to a distinct blue endpoint. Perform the blank determination.

Calculate the percentage of calcium (Ca) in the Sample taken:

Result = {[(V_S − V_B ) × M × F]/W} × 100

V_S = Titrant volume consumed by the Sample (mL)

V_B = Titrant volume consumed by the Blank (mL)

M = actual molarity of the Titrant (mmol/mL)

F = equivalency factor, 40.08 mg/mmol

W = Sample weight (mg)

Acceptance criteria: 8.2%–8.6% on the dried basis

Add the following:

5 IMPURITIES

Beta Alanine and Other Aminocarboxylic Acid Impurities

Sample: 8.000 g of Calcium Pantothenate

Blank: 100 mL of water and 25 mL of formaldehyde solution

Titrimetric system

(See Titrimetry 〈541〉.)

Mode: Direct titration

Titrant: 0.1 N sodium hydroxide VS

Endpoint detection: Potentiometric

Analysis: Dissolve the Sample in 40 mL of water and dilute with the same solvent to 100 mL. Add 25 mL of formaldehyde solution and titrate with Titrant. Perform the blank determination.

Calculate the percentage of β-alanine in the Sample taken:

Result = [(V_S − V_B ) × N × F/W] × 100

VS= Titrant volume consumed by the Sample (mL)

V_B = Titrant volume consumed by the Blank (mL)

N = actual normality of the Titrant (mEq/mL)

F = equivalency factor, 89.09 mg/mEq

W = Sample weight (mg)

Acceptance criteria: NMT 0.5%

Other Related Substances

Mobile phase and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 0.004 mg/mL of USP Calcium Pantothenate RS, 0.04 mg/mL of USP Sodium d-Pantoate RS, and 0.02 mg/mL of USP

Pantolactone RS in water

Sample solution: 4 mg/mL of Calcium Pantothenate in water

System suitability

Sample: Standard solution

[Note—The relative retention times for pantoic acid, pantolactone, and pantothenic acid are 0.5, 0.8, and 1.0, respectively.]

Suitability requirements

Resolution: NLT 3.0 between pantolactone and pantothenic acid peaks

Relative standard deviation: NMT 5.0% for pantoic acid, pantolactone, and pantothenic acid peaks

Analysis

Samples: Standard solution and Sample solution

Run time: 30 min

Calculate the percentage of pantoic acid in the portion of Calcium Pantothenate taken:

Result = (r_U /r_S) × (C_S /C_U )× (M_t1 /M_t2) × 100

r_U = peak area of pantoic acid from the Sample solution

r_S = peak area of pantoic acid from the Standard solution

C_S = concentration of USP Sodium d-Pantoate RS in the Standard solution (mg/mL)

C_U = concentration of Calcium Pantothenate in the Sample solution (mg/mL)

M_t1 = molecular weight of pantoic acid, 148.16

M_t2 = molecular weight of sodium pantoate, 170.14

Calculate the percentage of pantolactone in the portion of Calcium Pantothenate taken:

Result = (r_U /r_S) × (C_S /C_U ) x 100

r_U = peak area of pantolactone from the Sample solution

r_S = peak area of pantolactone from the Standard solution

C_S = concentration of USP Pantolactone RS in the Standard solution (mg/mL)

C_U = concentration of Calcium Pantothenate in the Sample solution (mg/mL)

Disregarding any peak due to beta alanine and other aminocarboxylic acid impurities with relative retention times below 0.2, calculate the

percentage of β-alanyl pantothenamide and any unspecified impurity in the portion of Calcium Pantothenate taken using the concentration of calcium pantothenate in the Standard solution:

Result = (r_U /r_S) × (C_S /C_U ) x 100

r_U = peak response of β-alanyl pantothenamide or any unspecified impurity from the Sample solution

r_S = peak response of pantothenic acid from the Standard solution

C_S = concentration of USP Calcium Pantothenate RS in the Standard solution (mg/mL)

C_U = concentration of Calcium Pantothenate in the Sample solution (mg/mL)

Acceptance criteria: See Table 1. The reporting threshold is 0.05%.

6 SPECIFIC TESTS

6.1 Alkalinity

Sample: 1.0 g

Analysis: Dissolve the Sample in 15 mL of carbon dioxide-free water in a small ask. As soon as the solution is complete, add 1.0 mL of 0.10N hydrochloric acid, and then add 0.05 mL of phenolphthalein TS.

Acceptance criteria: No pink color is produced within 5 s.

6.2 Loss on Drying 〈731〉

Analysis: Dry at 105° for 3 h.

Acceptance criteria: NMT 5.0%

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Calcium Pantothenate RS

USP Pantolactone RS

USP Sodium d-Pantoate RS